Purpose: The aim was to determine the echocardiographic features of patients with infective endocarditis, and to compare the findings in HIV positive versus HIV negative patients. Methods: This was a prospective study, conducted over three years using the modified Duke criteria in diagnoses. A control group of age-matched patients with clinical and echocardiographic evidence of valvular regurgitation, who did not satisfy the criteria and who underwent surgery was used in comparison. Results: During this period 91 patients were screened for infective endocarditis. 77 satisfied the criteria for a definite diagnosis of IE. Blood cultures were positive in 46% cases. The commonest organism was S. aureus. Most patients had advanced valve disruption with heart failure and a high peri-operative mortality. The clinical features in the two groups of patients was similar. The incidence of echocardiographic complications was 50.6% in the whole group. Except for leaflet aneurysms in four HIV positive cases, complications were not more frequent in this group. Conclusion: There was a high rate of culture negative cases in this study, probably related to prior antibiotic usage; in this setting the modified Duke criteria have diagnostic limitations. There was no difference in the clinical presentation of infective endocarditis between HIV positive and HIV negative patients. Leaflet aneurysms were more common in the HIV positive patients. / Thesis (M.Med.)-University of KwaZulu-Natal, 2008.

The metabolic syndrome (MS), consequent upon the pandemic of obesity and diabetes, is associated with an increased risk for cardiovascular (CV) disease. Development of sub-clinical cardiac structural and functional changes associated with CV disease risk factors may be detected on echocardiography. The extent to which these structural changes and CV risk factors are dependent on genetic factors is not clearly established. This project was designed to investigate the relationship between CV disease risk factors, cardiac structural and functional changes and underlying genetic abnormalities. Specifically, the risk factor profile and the presence of the MS were determined. This was then correlated with the echocardiographic findings and gene polymorphisms. Method: A randomly selected cohort of 1428 subjects from the Phoenix community was studied. Demographic data was collected using the WHO STEPS instrument. Blood samples for biochemistry and genetic analysis, together with anthropometric measurements, were collected. Blood pressure and echocardiography was performed on all subjects. The metabolic syndrome was classified according to the National Cholesterol Education Panel (NECP) Adult Treatment Panel III (ATP III) and International Diabetes Federation (IDF) criteria. The Lipoprotein Lipase and Human Paraoxonase-1 genes were genotyped on a Light Cycler 480 Real-Time PCR instrument, using allele-specific probes and sequencing. Results: There was a high prevalence of CV risk factors in this sample; particularly increased waist circumference (79%), obesity (64%) insulin resistance (58%) and hypertension (50%) across the age groups. This translated into a high prevalence of MS (38% using NCEP ATPIII and 46% using IDF criteria). There were significant echocardiographic differences between subjects with and without MS for chamber dimensions (p<0.001), left ventricular wall thickness (p<0.001) and mass (p<0.001), diastolic indices (E-wave {p<0.001}, trans-mitral ratio {p=0.017}) and sub-epicardial adipose tissue (SEAT) thickness (p<0.001). Stepwise multivariate analysis identified age (95% CI 0.975; 0.998), gender (95%CI 0.48; 0.9) and hypertension (95% CI 0.53; 0.99) as independent risk factors for diastolic abnormalities. Logistic regression identified age as the most significant contributor to diastolic abnormalities (OR=1.02; 95%CI 1.009; 1.03; Wald=13.4), followed by the waist circumference (OR=1.025; 95%CI 1.014; 1.037) and BMI (OR=1.075; 95% CI 1.035; 1.117). Genetic analysis showed significant associations between the heterozygous variant of Q192R genotype (PON-1 gene) and elevated HDL levels and also between this variant and obese women (p= <0.05). Conclusion: The high prevalence of CV risk factors and MS in this community has reached epidemic proportions. Although the MS was associated with significant remodelling of cardiac structure, alteration of diastolic indices and increased sub-epicardial adipose tissue thickness, BMI and waist circumference were stronger promoters of altered cardiac physiology. This augurs poorly for this population group unless intervention is introduced to address the markedly high prevalence of these culprit drivers. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2013.

Conventional echocardiographic parameters are currently used in determining the timing for surgery in patients with mitral regurgitation. Since brain natriuretic peptide (BNP) rises in response to ventricular muscle stretch, and is to detect early heart failure, we hypothesized that BNP would be activated in patients with regurgitant valvular heart disease and concomitant left ventricular dilatation. Aim/Objectives: We therefore studied the pattern of changes in NT-pro BNP in patients with chronic severe rheumatic mitral regurgitation who were undergoing mitral valve replacement and compared this with the newer modality of tissue Doppler imaging (TDI). Setting: Patients submitted to surgery were prospectively evaluated over 8 months at Inkosi Albert Luthuli Central Hospital, Department of Cardiology. Controls were obtained from the outpatients' follow-up clinic. Methods: Simultaneous quantification of the severity of mitral regurgitation (MR), left ventricular (LV) end systolic volume (ESV), left atrial (LA) volume and Doppler filling ratios (mitral (E)/annulus (Ea)) were performed at baseline in all patients and was repeated at 1-week and at the six-week follow-up visit in surgical patients. Results: Both groups were similar for age and gender and echo-Doppler parameters in all patients preoperatively except LA size (p< 0.01) and volume (p<0.004) which were more elevated in the surgical group. Mean NT-pro BNP levels were markedly elevated preoperatively (262 pmolll) in all surgical cases compared to controls (57 pmol/l; p=0.0001). NT-pro BNP levels increased further at one week post surgery (395 pmol/l) and subsided at the six week follow-up visit (94 pmol/I). These changes were accompanied by significant reduction in LA (p= 0.003) and LV chamber dimensions (EDD = 0.004) with an increase in the ejection fraction from 42% at one week to 52 % at six weeks. Four patients had abnormally elevated NT-pro BNP levels (>53pmol/l) at the 6-week follow-up visit. A ROC curve was constructed for all variables to separate surgical cases from controls. The area under the curve was highest for NT-pro BNP (sensitivity= 96%, specificity 45 %). Conclusion: 1. There was a significant difference in the left atrial chamber size and volume, as well as Em/Ea (TDI) and NT-proBNP levels preoperatively between the two groups. The lack of a significant difference in the LV parameters between surgical and control groups suggest an almost total reliance on symptoms in deciding the timing of surgery which was reflected by markedly elevated NT-pro BNP in all surgical patients. 2. Postoperatively, there was a significant reduction in LA and LV dimensions. 3. The high false positivity rate for NT-pro BNP suggests that the test is most likely reflecting early LV decompensation in the less symptomatic control patients who rightly need surgery. 4. Tissue Doppler indices had similar sensitivity but low specificity compared to NT-proBNP. 5. Serial estimations of NT-pro BNP may prove useful in selecting patients for surgery. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, 2007.

Objective: To determine the role of candidate gene polymorphisms in patients who sustained myocardial infarction at a young age and examine their relationship, if any, to risk factors. Since angiotensin II is known to play a pathophysiological role at the myocardial and vascular level, the genes to be studied are those regulating the renin angiotensin system and tissue metabolism. Design: The risk factors and genetic profile is described in 117 young Indians with myocardial infarction recruited over a period of thirty months (Dec 1997 - Jun 1999). Controls comprised 80 normal subjects with no clinical evidence of coronary heart disease (CHD) and with a normal effort response. The key features of this study are the selection of young subjects with myocardial infarction, (mean age 43 ± 6.8 years) in whom the possibility of a genetic basis for the disease was felt to be more likely since the confounding effect of age as a risk factor was reduced. Setting: Patients recruited 3 -12 months after myocardial infarction from Addington Hospital, Durban. This hospital subserves the Indian community in the north of Durban. The majority of patients were from the Phoenix settlement area. Results: 1. The clinical profile of the young Indian with myocardial infarction is a young man, slightly overweight with a high prevalence of risk factors, particularly smoking and diabetes, coupled with sedentary behaviour and risk-prone dietary patterns characterised by high red meat intake and low fruit and vegetable consumption, resulting in increased BMI and W/H ratios. 2. There were no differences in the patterns of gene polymorphism in the reninangiotensin system between the study and control groups. This finding extended across all candidate gene loci studied i.e. those involving aldosterone, G-protein, TGF-B and homocysteine metabolism. Serum triglycerides, haemoglobin AlC and urine microalbumin levels were elevated in the probands together with low HDL-C levels (p = 0.001). 3. A striking finding of this study was the substantial proportion of patients found to have diabetes mellitus, totalling 47% of the proband group. Of the 53 diabetic patients, (45 males and 8 females) four (3 males, 1 female) had impaired glucose tolerance. Cigarette smoking, a positive family history of hypertension/diabetes and a family history for premature CHD emerged as important risk predictors for MI. Conclusion: This study, the first to report candidate gene polymorphisms in young Indians with coronary heart disease, has shown no obvious association between the genetic loci studied and acute myocardial infarction. Instead a high prevalence of risk factors, particularly smoking and diabetes mellitus, coupled with coronary-prone behavioural patterns was observed. In the light of these findings, genome-wide screening of unaffected siblings of subjects with early onset CHD cannot be recommended in this population until common polymorphisms can be clearly identified as risk factors. Indeed this study again supports the dire need for early, school level, education in behavioural lifestyle patterns and disease predisposition. The Indian community is a very high-risk group who should be targeted, not for secondary, but for primordial disease prevention measures. The study does not rule out the role of other candidate gene polymorphisms in the pathogenesis of CHD in these subjects. The high prevalence of diabetes and insulin resistance suggests that studies of genes regulating glucose and lipid metabolism should be pursued. Such candidate genes should include genes for lipoprotein lipase and paraoxonase polymorphisms which may explain the dyslipidaemia patterns in this group. / Thesis (Ph.D.)-University of Natal, Durban, 2000.

Pulmonary dysfunction following cardiopulmonary bypass surgery is a widely explored complication and a multitude of factors have been implicated, including but not limited to: operative trauma; the cardiopulmonary bypass circuit; cardioplegia; the type of donor grafts utilised; anaesthesia and fluid administered. There is a paucity of information regarding the effect of cardioplegia on the lungs. No studies have previously investigated whether allowing cold-blood cardioplegic solution to enter the lung parenchyma, during the period of cardioplegia delivery, has an effect on the clinical outcome of lung function following cardiopulmonary bypass surgery. For this reason an original study was done to determine the effect of preventing cardioplegia from entering the lungs, by evacuating overflow of cardioplegia not drained via the atriocaval cannula, by using a pulmonary artery vent. A total of 403 patients admitted to undergo full cardiopulmonary bypass were screened and 142 patients who fitted the criteria for inclusion and provided informed consent took part in this prospective double blind randomised clinical trial. The control group underwent routine cardiopulmonary bypass grafting. The study group had the intervention of a pulmonary artery vent sutured in position at the time the heart was cannulated for bypass. During cardioplegia delivery the cardioplegia was removed via the atriocaval cannula in the control group (A) and via the atriocaval cannula and the pulmonary artery vent in the study group (B). Aside from this difference, the two groups were managed identically intra- and post-operatively. Outcomes which were compared included eight time measures of arterial blood gases; electrolytes and shunt fraction; bedside lung spirometry measures over five time periods; radiographic measures of atelectasis and effusion over three time points; as well as physiotherapy and hospitalisation requirements. Numerous other potentially extraneous variables were measured and compared in order to monitor homogeneity of the study samples. The consistency of the results within each group throughout the study provides strong evidence that the measurements taken were accurate. The use of standardised equipment and vigilant adherence to the protocol ensured no extraneous deviation. The internal validity of this study was therefore good and accurate. The findings of the study however brought into question a previously accepted belief that the pulmonary artery vent prevents the overflow of cardioplegia, not drained from the right atrium, from entering the lungs. There was no literature or previous studies to confirm or dispute this accepted ‘observation’ by cardiac surgeons that the cardioplegia does enter the lung parenchyma. To therefore validate the findings of the study a further four original studies were designed and initiated. The objective of these studies was to establish the efficacy of the pulmonary artery vent and to determine whether cardioplegia indeed circulates through the lung parenchyma or merely accumulates and ‘pools’. Technetium (Tc-99m), a radio labelled isotope was added to the cold blood cardioplegia solution prior to delivery in order to determine this. In the four sub-studies it was confirmed that the pulmonary artery vent is 90-100% effective in retrieving any cardioplegic solution not drained by the atriocaval cannulae, thus confirming the effectiveness of the pulmonary artery vent in preventing cold blood cardioplegic solution from entering the lungs. The findings of the main study confirmed that respiratory impairment after uncomplicated cardiopulmonary bypass, even in low risk patients, is relatively common, as within each group there was a significant change in outcome measures over time. Inter-group comparisons however showed these changes were not significant, with both groups deteriorating by the same degree post-operatively, therefore establishing that these changes were independent of the intervention of the pulmonary artery vent. In the control group, the cold blood cardioplegia solution that did not drain from the atriocaval cannula entered the lungs and circulated the lung parenchyma during cardiopulmonary bypass. The study group made certain that none, or very little, of the cold blood cardioplegia solution entered the lungs. The main findings of this study are therefore that pulmonary function and gas exchange, although markedly reduced following cardiac surgery, are not affected by placement and suctioning via a pulmonary artery vent during the time of cardioplegia delivery intraoperatively. Furthermore, these studies strongly suggest that cold blood cardioplegia solution is innocuous to the lungs / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, 2006.

No abstract available. / Thesis (M.D.)-University of Natal, 1973.